Recently there have been exciting research advances in neuroprotective therapies for ischemic stroke. In the past, the search for neu- roprotective agents has been fraught with failure at the clinical trials stage due...Recently there have been exciting research advances in neuroprotective therapies for ischemic stroke. In the past, the search for neu- roprotective agents has been fraught with failure at the clinical trials stage due to numerous factors, including subject heterogeneity and improper therapeutic windows （Tymianski, 2017）. Moreover, it is becoming clearer that the complex and evolving pathobiology of stroke requires multimodal therapeutic approaches capable of modulating the numerous axes that contribute to ischemia/reperfusion damage, rather than targeting a single axis （Bernstock et al., 2018a）. With the success of recent endovascular thrombectomy （EVT） trials, it has been suggested that clinical trials of EVT with adjunct neuroprotection can overcome past difficulties and maximize the effect size by using imaging to reduce patient heterogeneity （i. e., selecting those with large vessel occlusions, small ischemic cores, and good collateral circulation）, restoring perfusion using better EVT devices, and enrolling patients in the correct therapeutic window （i.e., when they still have salvageable brain tissue） （Tymianski, 2017）. Considering the opportunity that this represents for new, better clinical trials of neuroprotective agents, the search is on for high-potential compounds that may be investigated in these future studies.展开更多
Hypoxia-inducible factor-1 (HIF-1) has been recognized as an important cancer drug target. Many recent studies have provided convincing evidences of strong correlation between elevated levels of HIF-1 and tumor metast...Hypoxia-inducible factor-1 (HIF-1) has been recognized as an important cancer drug target. Many recent studies have provided convincing evidences of strong correlation between elevated levels of HIF-1 and tumor metastasis, angiogenesis, poor patient prognosis as well as tumor resistance therapy. It was found that hypoxia (low O<sub>2</sub> levels) is a common character in many types of solid tumors. As an adaptive response to hypoxic stress, hypoxic tumor cells activate several survival pathways to carry out their essential biological processes in different ways compared with normal cells. Recent advances in cancer biology at the cellular and molecular levels highlighted the HIF-1α pathway as a crucial survival pathway for which novel strategies of cancer therapy could be developed. However, targeting the HIF-1α pathway has been a challenging but promising progresses have been made in the past twenty years. This review summarizes the role and regulation of the HIF-1α in cancer, and recent therapeutic approaches targeting this important pathway.展开更多
Two-dimensional graphene offers interesting electronic,thermal,and mechanical properties that are currently being explored for advanced electronics,membranes,and composites.Here we synthesize and explore the biologica...Two-dimensional graphene offers interesting electronic,thermal,and mechanical properties that are currently being explored for advanced electronics,membranes,and composites.Here we synthesize and explore the biological applications of nano-graphene oxide(NGO),i.e.,single-layer graphene oxide sheets down to a few nanometers in lateral width.We develop functionalization chemistry in order to impart solubility and compatibility of NGO in biological environments.We obtain size separated pegylated NGO sheets that are soluble in buffers and serum without agglomeration.The NGO sheets are found to be photoluminescent in the visible and infrared regions.The intrinsic photoluminescence(PL)of NGO is used for live cell imaging in the near-infrared(NIR)with little background.We found that simple physisorption viaπ-stacking can be used for loading doxorubicin,a widely used cancer drug onto NGO functionalized with antibody for selective killing of cancer cells in vitro.Owing to its small size,intrinsic optical properties,large specifi c surface area,low cost,and useful non-covalent interactions with aromatic drug molecules,NGO is a promising new material for biological and medical applications.展开更多
文摘Recently there have been exciting research advances in neuroprotective therapies for ischemic stroke. In the past, the search for neu- roprotective agents has been fraught with failure at the clinical trials stage due to numerous factors, including subject heterogeneity and improper therapeutic windows （Tymianski, 2017）. Moreover, it is becoming clearer that the complex and evolving pathobiology of stroke requires multimodal therapeutic approaches capable of modulating the numerous axes that contribute to ischemia/reperfusion damage, rather than targeting a single axis （Bernstock et al., 2018a）. With the success of recent endovascular thrombectomy （EVT） trials, it has been suggested that clinical trials of EVT with adjunct neuroprotection can overcome past difficulties and maximize the effect size by using imaging to reduce patient heterogeneity （i. e., selecting those with large vessel occlusions, small ischemic cores, and good collateral circulation）, restoring perfusion using better EVT devices, and enrolling patients in the correct therapeutic window （i.e., when they still have salvageable brain tissue） （Tymianski, 2017）. Considering the opportunity that this represents for new, better clinical trials of neuroprotective agents, the search is on for high-potential compounds that may be investigated in these future studies.
基金partially supported by the NIH grant 1R01CA148706funds from the University of Tennessee Health Science Center, College of Pharmacy
文摘Hypoxia-inducible factor-1 (HIF-1) has been recognized as an important cancer drug target. Many recent studies have provided convincing evidences of strong correlation between elevated levels of HIF-1 and tumor metastasis, angiogenesis, poor patient prognosis as well as tumor resistance therapy. It was found that hypoxia (low O<sub>2</sub> levels) is a common character in many types of solid tumors. As an adaptive response to hypoxic stress, hypoxic tumor cells activate several survival pathways to carry out their essential biological processes in different ways compared with normal cells. Recent advances in cancer biology at the cellular and molecular levels highlighted the HIF-1α pathway as a crucial survival pathway for which novel strategies of cancer therapy could be developed. However, targeting the HIF-1α pathway has been a challenging but promising progresses have been made in the past twenty years. This review summarizes the role and regulation of the HIF-1α in cancer, and recent therapeutic approaches targeting this important pathway.
基金by NIH-NCI funded CCNE TR at Stanford University.We are grateful to Drs.Alice Fan and Dean Felsher for providing the antibodies used in this work.
文摘Two-dimensional graphene offers interesting electronic,thermal,and mechanical properties that are currently being explored for advanced electronics,membranes,and composites.Here we synthesize and explore the biological applications of nano-graphene oxide(NGO),i.e.,single-layer graphene oxide sheets down to a few nanometers in lateral width.We develop functionalization chemistry in order to impart solubility and compatibility of NGO in biological environments.We obtain size separated pegylated NGO sheets that are soluble in buffers and serum without agglomeration.The NGO sheets are found to be photoluminescent in the visible and infrared regions.The intrinsic photoluminescence(PL)of NGO is used for live cell imaging in the near-infrared(NIR)with little background.We found that simple physisorption viaπ-stacking can be used for loading doxorubicin,a widely used cancer drug onto NGO functionalized with antibody for selective killing of cancer cells in vitro.Owing to its small size,intrinsic optical properties,large specifi c surface area,low cost,and useful non-covalent interactions with aromatic drug molecules,NGO is a promising new material for biological and medical applications.
